Mifepristone Notably Reduces HbA1c in Treatment Phase of CATALYST Trial

Ralph DeFronzo, MD

Credit: LinkedIn

Positive results from the treatment phase of the randomized, double-blind, placebo-controlled Phase 4 CATALYST trial demonstrated the benefit of mifepristone (Korlym) in patients with hypercortisolism (Cushing’s syndrome) and difficult-to-control type 2 diabetes (T2D).¹

Announced by Corcept Therapeutics Incorporated, on December 12, 2024, mifepristone achieved the primary endpoint in the treatment phase of the trial, exhibiting a clinically meaningful and statistically significant improvement in hemoglobin A1c (HbA1c).

“CATALYST’s first part showed that hypercortisolism is much more common than previously assumed,” investigator Ralph DeFronzo, MD, chief of the Diabetes Division and professor of medicine at UT Health San Antonio, said in a statement. “The results announced today show that [mifepristone] is a safe and effective treatment option. Reductions in HbA1c of this magnitude are of great clinical benefit.”

Caused by the excessive activity of cortisol, symptomatic manifestations of hypercortisolism include hypertension, central obesity, elevated blood sugar, and difficult-to-control T2D.² Hypercortisolism can impact every organ system in the body and can be lethal if left untreated. Mifepristone is a cortisol receptor blocker indicated to control hyperglycemia secondary to hypercortisolism in adults with endogenous hypercortisolism who have T2D or glucose intolerance, and have failed surgery or are not surgical candidates.¹

CATALYST is a prospective Phase 4 trial consisting of two parts. CATALYST enrolled 1055 patients across 36 sites in the US, making it the largest study to evaluate the prevalence of hypercortisolism in patients with difficult-to-control T2D, defined as HbA1c ≥7.5 despite receiving optimal therapies, including GLP-1 agonists.

According to data from the first part of the trial, hypercortisolism is exceedingly common, with approximately 1 in 4 patients in CATALYST exhibiting endogenous hypercortisolism.³ Of these patients from Part 1, 23.8% were eligible to enter the treatment phase of CATALYST.

In the treatment phase, 136 patients were randomized 2:1 to receive mifepristone or placebo for 24 weeks. Reduction in HbA1c between each group served as the trial’s primary endpoint.

Upon analysis, individuals treated with mifepristone achieved a clinically meaningful and statistically significant improvement in HbA1c.¹ These data showed a decrease from the baseline of 1.47% with mifepristone, compared with 0.15% for placebo (placebo-adjusted reduction, 1.32%; P <.0001). Safety remained consistent with the label, with no new safety signals or adverse events identified in the data.

Corcept Therapeutics announced the complete results from CATALYST will be presented at a medical conference next year.

“They are particularly compelling, given that the patients in CATALYST have been receiving our best therapy – but continued to experience serious disease,” DeFronzo added.¹ “These findings should prompt expanded screening for hypercortisolism, more effective treatment, and better health outcomes for patients who are struggling today.”

References

1. _{Corcept announces positive results in treatment phase of catalyst trial in patients with hypercortisolism (Cushing’s syndrome) and difficult-to-control diabetes. Corcept Therapeutics, Incorporated. December 12, 2024. Accessed December 12, 2024. https://ir.corcept.com/news-releases/news-release-details/corcept-announces-positive-results-treatment-phase-catalyst.}
2. _{Chaudhry HS, Singh G. Cushing Syndrome. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470218/}
3. _{Corcept announces presentation of results from prevalence phase of catalyst clinical trial at American Diabetes Association’s Scientific sessions. Corcept Therapeutics, Incorporated. June 24, 2024. Accessed December 12, 2024. https://ir.corcept.com/news-releases/news-release-details/corcept-announces-presentation-results-prevalence-phase-catalyst.}